Genetic defects in pregnenolone synthesis.

The pregnenolone synthesis is the first step in the biosynthesis of all steroid hormones. The disruption of this step is known to result in congenital lipoid adrenal hyperplasia (CLAH), a most severe form of congenital adrenal hyperplasia. CLAH was first demonstrated to be caused by mutations in the STAR gene encoding steroidogenic acute regulatory protein (StAR). Now genetic and phenotypic variations have been elucidated in pregnenolone synthesis defects; mutations in the CYP11A1 gene encoding cholesterol side-chain cleavage enzyme (SCC) also cause disordered pregnenolone synthesis, and STAR mutations do not necessarily results in typical CLAH. To define these conditions precisely, pathophysiological diagnoses, such as StAR deficiency and SCC deficiency, are more likely to be appropriate than the histopathological diagnosis like CLAH.